Anti-Vector Immunoglobulin Induced by Retroviral Vectors

Replication-incompetent retroviruses have been employed as gene therapy vectors in experimental settings for more than a decade. More recently, these vectors have been tested in the clinic as immunotherapeutic agents and anticancer agents. One potential problem with the use of such vectors is the possible development of immune responses directed against the vector particles themselves. Here, we examine immunoglobulin (Ig) responses specific for retroviral vectors derived from murine leukemia virus (MLV). Anti-MLV Ig is seen following intramuscular (i.m.) administration of retroviral vectors in mice, and in nonhuman primates; as expected, these responses are dependent upon the vector dose delivered. Furthermore, serum from vector-treated animals is capable of partially neutralizing vector-mediated transduction of target cells in an in vitro assay. Nevertheless, even in the presence of significant levels of anti-vector Ig in vivo, i.m. administration of retroviral vector is still capable of driving both Ig and cytotoxic T lymphocyte (CTL) responses specific for vector-encoded gene products. This work suggests that although retroviral vectors may readily induce immune responses directed against the vector particles themselves, such responses will not significantly affect the efficiency of these vectors in an immunotherapeutic protocol.

Overview summary

We have examined the immunoglobulin (Ig) response directed against retroviral vector particles in rodent and non-human primate models.In all animals examined to date, intramuscular (i.m.) administration of retroviral vector induces strong anti-vector Ig responses, in a dose-dependent fashion. Although such anti-vector Ig is capable of neutralizing vector in an in vitro assay, no adverse effect on vector efficacy was seen following repeated i.m. administration.